Method development was completed for a strategy to access a novel pyrimidine-fused heterocyclic scaffold. The key step for this synthetic route entails an intramolecular inverse electron demand hetero-Diels-Alder reactio...Method development was completed for a strategy to access a novel pyrimidine-fused heterocyclic scaffold. The key step for this synthetic route entails an intramolecular inverse electron demand hetero-Diels-Alder reaction of imines or iminiums formed in situ from allylaminopyrimidinealdehydes 3 and anilines. The reactions provided exclusively cis-configuration products 6. Products 6 were readily precipitated in the reaction solution in good to excellent yields. Further transformations of the phenylthio group were demonstrated by an oxidation and subsequent nucleophilic substitution sequence. The synthetic strategy provides an efficient way to access libraries of the tetracyclic pyrimidine-fused heterocycles that can be explored for potential pharmaceutical or biological activities.
An efficient, convenient, one-pot synthesis of 2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazolin-5(1H)-one and 2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazoline-1,5-dione was accomplished in good yields via the novel reductive cycl...An efficient, convenient, one-pot synthesis of 2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazolin-5(1H)-one and 2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazoline-1,5-dione was accomplished in good yields via the novel reductive cyclization of 2-nitrobenzamides with haloketones or keto acids mediated by SnCl(2).2H(2)O system. A variety of substrates can participate in the process with good yields, making this methodology suitable for library synthesis in drug discovery efforts.
An efficient and simple route for preparation of substituted 1,5-benzodiazepine-2-one containing peptoid backbone is presented. The classical Ugi reaction is considerably extended by application of o-phenylenediamine and...An efficient and simple route for preparation of substituted 1,5-benzodiazepine-2-one containing peptoid backbone is presented. The classical Ugi reaction is considerably extended by application of o-phenylenediamine and diketene as amine and oxo component. 1,3-Dihydro-1,5-benzodiazepine-2-one is generated in situ from these two building blocks combined with isocyanide and aromatic or aliphatic carboxylic acid to assemble the multifunctionalized titled scaffold in high yields. The reaction is performed in the mixture of toluene/CH(2)Cl(2) under reflux condition without catalyst. Conformational isomerism is seen in the solution phase because of restricted free rotation around amide and C-CO bands due to steric bulk of substitutions. In single crystal state, the product is found to possess dimeric structure arising from intermolecular hydrogen bonding.
A fast and highly efficient copper-catalyzed multicomponent synthesis of 1,4-dihydropyridines under microwave irradiation is described. The protocol utilizes mild reaction conditions with low catalytic loading, leading t...A fast and highly efficient copper-catalyzed multicomponent synthesis of 1,4-dihydropyridines under microwave irradiation is described. The protocol utilizes mild reaction conditions with low catalytic loading, leading to high yields. This methodology provides us with biologically active 1,4-dihydropyridine library for medicinal chemistry applications.
J Comb Chem
· 2010 Jul · PMID 20527770
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Full text
Starting with resin-bound glutamic acid, an efficient synthesis of N-substituted pyrrolidinones is described, using the Ugi four-component reaction (U-4CR). The same methodology is employed to produce N-substituted pyrro...Starting with resin-bound glutamic acid, an efficient synthesis of N-substituted pyrrolidinones is described, using the Ugi four-component reaction (U-4CR). The same methodology is employed to produce N-substituted pyrrolidinone tethered N-substituted piperidines.
A new concise, facile, and efficient method for the synthesis of 3-hydroxy-5,6-diphenylpyrazolo[3,4-b]pyridine derivatives has been described. The cyclocondensation of isoflavones with 3-amino-5-hydroxypyrazole in the pr...A new concise, facile, and efficient method for the synthesis of 3-hydroxy-5,6-diphenylpyrazolo[3,4-b]pyridine derivatives has been described. The cyclocondensation of isoflavones with 3-amino-5-hydroxypyrazole in the presence of sodium methoxide gave fused heteroaromatic 3-hydroxy-5,6-diphenylpyrazolo[3,4-b]pyridines in moderate to good yields.
The dyes Methyl Calcein Blue, Arsenazo I, and Xylenol Orange, and the metal salts CuCl(2) and NiCl(2) were used to generate colorimetric sensors for peptides. Two different approaches were followed: (1) Sensors based on...The dyes Methyl Calcein Blue, Arsenazo I, and Xylenol Orange, and the metal salts CuCl(2) and NiCl(2) were used to generate colorimetric sensors for peptides. Two different approaches were followed: (1) Sensors based on dynamic combinatorial libraries of metal-dye complexes were created by mixing dyes with metal salts in one pot. The optical response of these libraries was analyzed by measuring the spectral changes of the mixtures upon addition of the peptide analytes at six selected wavelengths. (2) Sensor arrays were created from six different metal-dye combinations. The six individual sensors were analyzed at one wavelength, and the resulting data was used as the input for a multivariate analysis. Both types of sensors were evaluated for their ability to differentiate 13 different di- and tripeptides. The sensors based on dynamic combinatorial libraries gave in most cases better results than the sensor array. Furthermore it was found that libraries of intermediate complexity perform best as sensors.
Two series of new compounds with the general formula 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles and their isosteric 2-imino derivatives were synthesized by the multicomponent reaction of the appropriate acetoph...Two series of new compounds with the general formula 4,6-diaryl-2-oxo-1,2-dihydropyridine-3-carbonitriles and their isosteric 2-imino derivatives were synthesized by the multicomponent reaction of the appropriate acetophenone, aromatic aldehyde, ammonium acetate, and malononitrile or ethyl cyanoacetate. The products were obtained with excellent yields. The prepared compounds were evaluated for their in vitro ability to inhibit p38 alpha-MAP kinase. Several compounds showed p38 MAP kinase inhibitory properties with IC(50) as low as 0.07 microM. This is the first time to report compounds with such scaffold as p38 alpha-MAP kinase inhibitors. This asserts the potentiality of multicomponent reactions in drug discovery.
In this study, a divergent and practical solid-phase parallel diversity-oriented synthesis (DOS) strategy was successfully applied for the construction of five discrete core skeletons embedded with privileged benzopyrany...In this study, a divergent and practical solid-phase parallel diversity-oriented synthesis (DOS) strategy was successfully applied for the construction of five discrete core skeletons embedded with privileged benzopyranyl substructure. The diversity of these core skeletons was expanded through the introduction of various substituents at the R, R(1), and R(2) positions from a single key intermediate in five different pathways. More importantly, we efficiently maximized the molecular diversity through the transformation of the core skeleton itself by using the library-to-library concept and created a distinctively different collection of small molecules with the same building blocks. A 434-member polyheterocyclic benzopyran library was constructed on a scale of about 10 mg with the potential for further diversification. Without further purification, the average purity of the library is 85%.
A novel and efficient one-pot synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]quinoline]dione, spiro[furo[3,4-e]pyrazolo[3,4-b]pyridine-4,3'-indoline]dione, and spiro[indeno[2,1-e]pyrazolo[3,4-b]pyridine-4,3'-indoline]di...A novel and efficient one-pot synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]quinoline]dione, spiro[furo[3,4-e]pyrazolo[3,4-b]pyridine-4,3'-indoline]dione, and spiro[indeno[2,1-e]pyrazolo[3,4-b]pyridine-4,3'-indoline]dione derivatives via three-component reaction of isatin, 5-amino-3-methylpyrazole, and 1,3-dicarbonyl compounds in aqueous medium is described. The advantages of this method include high efficiency, mild reaction conditions, convenient operation, and environmentally benign conditions.
The thiol-disulfide dynamic interchange reaction mediated by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was extensively studied. By this synthetic method sulfides can be prepared successfully within seconds in high yields...The thiol-disulfide dynamic interchange reaction mediated by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was extensively studied. By this synthetic method sulfides can be prepared successfully within seconds in high yields at room temperature from stable and readily available disulfides and an alkylating agent. The method was further demonstrated to efficiently produce benzofused nitrogen-sulfur heterocycles with high skeletal diversity in a one-pot process.
Practical and efficient methods have been developed for the synthesis of 4,6,8,9-tetrasubstituted 8,9-dihydro-5H-pyrimido[4,5-e][1,4]diazepin-7(6H)-ones from 4,6-dicholoropyrimidine aldehyde, N-substituted amino acid est...Practical and efficient methods have been developed for the synthesis of 4,6,8,9-tetrasubstituted 8,9-dihydro-5H-pyrimido[4,5-e][1,4]diazepin-7(6H)-ones from 4,6-dicholoropyrimidine aldehyde, N-substituted amino acid esters, and amines in five steps. This synthetic strategy is based on suitably substituted pyrimidines as bis-electrophilic species reacting with various amines to construct the pyrimido[4,5-e][1,4]diazepine core with a strategically anchored functional group for further derivatization. The utility of this methodology was demonstrated through the preparation of a 33-membered library of representative 8,9-dihydro-5H-pyrimido[4,5-e][1,4]diazepin-7(6H)-ones in good to excellent yields.
A versatile protocol for the preparation of a library of 5,6-(het)bisarylated imidazo[1,2-b][1,2,4,5]tetrazines is described. Target compounds were obtained in fairly good yields, starting from ethoxy-7-(4-methoxyphenyl)...A versatile protocol for the preparation of a library of 5,6-(het)bisarylated imidazo[1,2-b][1,2,4,5]tetrazines is described. Target compounds were obtained in fairly good yields, starting from ethoxy-7-(4-methoxyphenyl)imidazo[1,2-b][1,2,4,5]tetrazine and a large panel of bromoaryl derivatives, using palladium catalysis under microwave irradiation. Compatibility with various chemical groups and heterocycles was proven. Steric and electronic effects do not have any effect on the efficiency of the reaction. Purifications were performed without any difficulties, and the structure of a final compound was proven by crystal X-ray diffraction studies.
A series of 4-aza-podophyllotoxin derivatives have been synthesized regioselectively via the three-component reaction of aldehydes, aromatic amines, and tetronic acid catalyzed by l-proline. This method has the advantage...A series of 4-aza-podophyllotoxin derivatives have been synthesized regioselectively via the three-component reaction of aldehydes, aromatic amines, and tetronic acid catalyzed by l-proline. This method has the advantages of high yield, high regioselectivity, extensive adaptability, easy operation, and environmental friendliness. These compounds were also investigated in vitro, and some were found to have good anticancer activity.
A new iodine-promoted domino reaction of 2-aminochromene-3-carbonitriles with various isocyanates is described, and a set of polyfunctionalized N-substituted 2-aminoquinoline-3-carbonitriles with high regioselectivity we...A new iodine-promoted domino reaction of 2-aminochromene-3-carbonitriles with various isocyanates is described, and a set of polyfunctionalized N-substituted 2-aminoquinoline-3-carbonitriles with high regioselectivity were successfully synthesized under microwave heating. In this reaction, the ring-opening/recyclization process occurs unexpectedly at the ring of 4H-pyran with different isocyanates.
To study the synergistic effect on the acidity and activity of Si-Al-Zr ternary oxide system, the mixture design of experiments was applied to prepare the ternary oxides by a sol-gel method, and rapid screening on dehydr...To study the synergistic effect on the acidity and activity of Si-Al-Zr ternary oxide system, the mixture design of experiments was applied to prepare the ternary oxides by a sol-gel method, and rapid screening on dehydration of isopropanol and Friedel-Crafts reaction was conducted to determine the activities. These activities, amount of acid site determined by pyridine pulse, and specific surface area, were correlated with the oxide composition by means of support vector machine. Clear synergy among the Si-Al-Zr was observed on the acidic character and the surface area, whereas no synergy between Al-Zr was observed on the catalytic activities. Multiple regression was then conducted to find a relationship between the activities and the characters. The term of Si molar fraction in the oxide was essential for good regression, and acid strength determined by peak temperature of NH(3) desorption was related to the Si fraction. Thus, simple and rapid technique for activity test and characterization can be integrated by means of support vector machine and multiple regression, and some insights of the active site were obtained.
A combinatorial chemistry method was used to synthesize and screen (Y(x)Lu(1-x-y))(3)Al(5)O(12):Ce(3y) green-yellow phosphors. The material libraries were obtained using an inkjet delivery system and screened for their f...A combinatorial chemistry method was used to synthesize and screen (Y(x)Lu(1-x-y))(3)Al(5)O(12):Ce(3y) green-yellow phosphors. The material libraries were obtained using an inkjet delivery system and screened for their fluorescence under an ultraviolet light of 365 nm. The optimized composition was identified to be (Y(0.2)Lu(0.788))(3)Al(5)O(12):Ce(3+)(0.036). Scale-up experiments confirmed that the optimized composition of the phosphor showed the highest luminescence intensity and an excellent scintillation performance with a short decay time (<60 ns). The results indicated that the (Y(x)Lu(1-x-y))(3)Al(5)O(12):Ce(3y) could be potentially useful as green-yellow phosphors for ceramic scintillators.
A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reac...A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.